1. Field of the Invention
The present invention is directed to a method for measuring perfusion of cerebrospinal fluid in the brain, and in particular to such a method employing magnetic resonance techniques.
2. Description of the Prior Art
The cerebrospinal fluid is a clear, colorless fluid whose composition consists of glucose, urea, proteins and salts in addition to some white blood cells. Cerebrospinal fluid is secreted by the vascular structures (choroid plexus) within the brain ventricles, but differs considerably in composition from plasma, which is the liquid portion of blood.
The cerebrospinal fluid layer around and inside the brain, and around the spinal cord, functions as a cushion against jarring or sudden shocks. The cerebrospinal fluid also circulates nutritive substances filtered from blood.
The formation of cerebrospinal fluid is continuous, and it circulates from the top to the bottom of the brain. The direction of flow is from the lateral ventricles to the third ventricle of the brain, through the aqueduct of Sylvius and the fourth ventricle, and then to the arachnoid space, in which it circulates around the brain and spinal cord.
At the base of the brain, the sub-arachnoid space widens in various areas to form so-called basal cisterns. The cerebrospinal fluid eventually is absorbed back into the general venous circulation via the arachnoid villi, which project into the various venous sinuses of the brain.
The amount of cerebrospinal fluid formed and the amount reabsorbed into the venous circulation result in a substantially constant volume of circulating fluid being maintained.
Although the absorption of cerebrospinal fluid is related proportionally to fluid pressure, the rate of formation of the cerebrospinal fluid is not. If there is increased production, decreased absorption, or some type of flow blockage, an increased accumulation of fluid within the ventricles will result. Anything which will increase the volume of fluid in the brain, such as a volume-occupying mass (tumor or hematoma or edema of the brain) will cause an increase in pressure within the system, since the rigid walls of the skull cannot expand. A damming of the venous circulation due to an obstruction or venous stasis (sluggish venous circulation) has a similar effect, since the free absorption of the cerebrospinal fluid into the venous sinuses is blocked.
Increased intracranial pressure occurs as a result of most head injuries, and can be responsible for serious morbidity and mortality. Conventionally, cerebrospinal fluid pressure is monitored by measuring pressure within the cerebrospinal fluid system, such as by a lumbar puncture with manometric readings. Lumbar puncture, however, has spinal cord damage risks associated therewith, and is not recommended to be routinely done for most head injuries.
A need exists for being able to obtain a quantitative analysis of the fluid exchange between the ventricles and other volumes filled with cerebrospinal fluid as well as a quantitative analysis of the flow of cerebral spinal fluid. Techniques for obtaining such a quantitative analysis, however, currently do not exist. Cerebrospinal fluid is not sufficiently radio-opaque to be observable with sufficient detail in x-rays, and since cerebrospinal fluid, like the surrounding tissue, contains a relative high density of hydrogen atoms, it is not readily distinguishable from surrounding tissue in a conventional image obtained by magnetic resonance techniques.
Although the use of intravenously administered contrast agents is known in the context of magnetic resonance imaging for producing detailed images of vascular structures, cerebrospinal fluid participates only very slightly in metabolism, so that intravenously administered contrast agents only minimally transfer from blood to the cerebrospinal fluid, if at all. Moreover, currently known intravenous contrast agents, such as Gd-DPPA, blood pool agents, and micro-bubbles, would remain in the brain for an unacceptably long period of time after being injected.
It is an object of the present invention to provide a method employing magnetic resonance imaging to produce a quantitative analysis of the exchange of cerebrospinal fluid between the brain ventricles and other volumes filled with cerebrospinal fluid and/or a quantitative analysis of the flow of cerebrospinal fluid.
This object is achieved in accordance with the present invention in a method wherein a suitable contrast agent is directly injected into fluid-filled spaces of the brain, in a volume of interest, via a minimally invasive access, and to quantitatively and time-dependently investigate the distribution and the outflow of this contrast agent into the other fluid-filled spaces in the volume of interest by means of a magnetic resonance examination. The magnetic resonance examination can be limited to the volume of interest, or can encompass a larger anatomical volume.
The contrast agent can be administered via an access route that has been previously surgically created for other purposes, or through a minimally invasive access route which is surgically created solely for this purpose.
The concentration of the contrast agent in the volume or volumes can be investigated on the basis of one or more magnetic resonance examinations with a time spacing therebetween.